Mod 3 & 4

• The primary immune response to an antigen occurs on the first occasion it is encountered. During this response, the adaptive immune system equips the body with defences such that if the same antigen is encountered again a stronger secondary response usually ensues that is so effective we don't get sick.
• Primary first time

  • takes a week for adaptive immunity to kick in
  • naive lymphocytes have to encounter antigen
  • become active and proliferate and differentiate
  • development of memory lymphocytes
  • long live and recognise antigen
• secondary response stronger response due to memory lymphocytes
• Abnormal Secondary response

  • Inappropriate response that can cause damage
  • Allergen pick up by dendrite
  • anitgen presenting
  • eat pathogen and antigen
  • active cells (t-cells)
  • connection with innate and adaptive
• Dendritic cells

  • periphery dedrite eat antigen
  • phenotype changes and activated
  • digets antigen
  • present fragment of antigen on surface (MHC)
  • present MHC to naive lymphocytes
  • naive lymphocytes reside in lymph node
  • T-cell receptor recognise MHC and becomes activated
  • proliferate and active into effector T-cells
• Immune Cells

  • Neutrophil
  • most abundant
  • lobe nuclei
  • phagocyctosis and granules that can kill microbes, release DNA and ensmear bacteria
• • Basophil
  • granules which results in tissue specific response
• • monocytes
  • horse shoe nuclei
  • precursor to marcophage
• • marcophages
  • contribute to inflammation
  • large
  • receptors that recognise microbes
  • produce cytokines
  • influence other immune cells
  • phagocytic
  • functional heterogenous
• • Lymphocytes
  • Big nuclei little cytoplams
  • Helper T cells
  • TH2 in allergies
  • Effector T cells
• • Plasma cells
  • produce antibodies
  • lots of mitochondria
  • need a lot of energy
• • NK cell
  • innate immune
  • ADCC, antibody dependent cell mediate cytotoxicity
• • Mast cell
  • type 1 hypersensitive
  • release granules
  • allergic reaction symptoms
  • long lived
• Antibodies:

  2 heavy and 2 light chains, 2 domains Fab (antigen binding very variable) and Fc (interacts with the immune system on FC receptors)
• Types of antibodies varies by heavy chain isotopes

  • IgM, Type 2 and 3
  • IgD
  • IgG, Type 2 and 3
  • IgE, Type 1
  • IgA
• IgE-mediated hypersensitvity/allergy

  Type I or IgE-mediated hypersensitivity reactions occur in people that produce IgE antibodies against normally innocuous allergens in the environment. This is typically the result of an unwanted type 2 or Th2 immune response that is characterised by high titres of allergen-specific IgE antibody being produced.
• Sensitization stage of IgE-mediated hypersensitivity

  Allergic reactions occur in individuals because they have become sensitised to an allergen. However, an important event is the induction of a type 2 or Th2 immune response that stimulates IgE antibody production. Allergen-specific IgE antibodies then coat the surface of mast cells by binding to antibody receptors on their surface called FceRs, sensitising them for the effector stage when the allergen is encountered again.
• First Encounter:

  1. Allergen Enters
  2. Allergen phagocytosed by dendritic cell
  3. Dendrite travel to lymph node
  4. Educated the Naive T cells through recognise of peptide on dedrites. Differentiate into Th2 cells which active B cells
  5. Cells travel to the infection site
  6. Th2 release cytokines (IL-4,5,13) that act on plasma cells to produce IgE
  7. IgE bind to mast cells (FceRs) and mast cells become sensitised
  8. Excess antibodies taken up by blood
  9. Antibodies sensitise basophils
  10. The antibodies sensitise other mast cells in different locations
• Second Encounter:

  1. Allergen enetrs
  2. binds to IgE on mast cells
  3. Mast cells release granules with histamine
  4. Mast cells release cytokines/chemokines
  5. Mast cells recruit additional cells
  6. Tissue specific response
  7. gastrointestinal tract
  8. increase fluid secretion and peristalsis
  9. Vomiting
  10. Diarrhoea
  11. eyes, nose, and airways
  12. decreased diameter, increased mucous
  13. wheezing, cough, phlegm
  14. sneezing
  15. Blood vessels
  16. increase blood flow and permeability
  17. fluid in tissues
  18. hypotension potentially leading to anaphylactic shock
  19. The mast cell break down releases platelet activating factor
• Late phase response

  The late phase response occurs some 4-6 hours after the initiation of the immediate response and is caused by the continued release of mast cell mediators and the combined actions of vasoactive and chemoattractant compounds that dilate blood vessels and stimulate the recruitment of other immune cells leading to edema (swelling).
• Type II hypersensitivity

  Type II hypersensitivities are mediated by IgG or IgM antibodies that bind to cell surface antigens. Antibody-opsonised cells are then recognised by leukocytes through specific Fc receptors leading to phagocytosis or nonphagocytic killing through a particular cytotoxic mechanism called antibody-dependent cell-mediated cytotoxicity (ADCC).
• Goodpasture’s syndrome, symptoms in kidney, G.B.M the immune system attacks the G.B.M. Death of kidney cells
• Type III hypersensitivity

  Type III hypersensitivities are also called immune complex-mediated hypersensitivities. This type of hypersensitivity reaction occurs when immune complexes (antigen-antibody complexes), that often form in the circulation, become deposited in susceptible tissues (e.g. the kidney) and cause inflammation and tissue destruction.
• Systemic lupus erythematosus, autoantigen recognise self antigens. Drive inflammation and tissue destruction. Activate complement, anaflatoxins recruit neutrophils and damage tissue
• Autoimmunity


  The immune system recognising self-antigens that can lead to immune responses against its own healthy cells and tissues
• Autoimmune diseases


  Diseases that result from these inappropriate immune responses against self
• Central tolerance


  Lymphocytes are educated to 'ignore' self-antigens when they are first generated
• Peripheral tolerance


  Mechanisms that exist to prevent the activation of self-reactive lymphocytes should they escape into the periphery
• Self-tolerance mechanisms fail


  Autoimmune diseases develop
• Immunological tolerance is a state of unresponsiveness to an antigen.

  • Lymphocyte
  • activated- immune response
  • inactivated/eliminated- tolerance
  • Self-reactive
  • respond to self-antigens
• If failure to remove self reactive can lead to autoimmune diseases.
• When a lymphocyte encounters an antigen it can either be activated, leading to an immune response, or inactivated/eliminated, leading to tolerance.
• Self-reactive lymphocytes that have the potential to respond to self-antigens (or autoantigens) are called autoreactive lymphocytes, some of which can generate autoantibodies against self-antigen when activated.
• All individuals possess some lymphocytes that have a degree of autoreactivity and low-affinity autoantibodies are part of our normal antibody spectrum. If immunological tolerance mechanisms fail to remove or control self-reactive lymphocytes autoimmune diseases can occur if the resulting autoimmune response leads to pathology.
• Tolerance to self-antigens is achieved in 2 main ways: central or peripheral tolerance
• Central tolerance


  Also known as clonal deletion, is the deletion of strongly self-reactive T and B cells during development and occurs in the primary lymphoid organs, the thymus for T cells and the bone marrow for B cells
• Antigen receptors (T and B cell receptors) are generated through random somatic rearrangement, resulting in a huge repertoire of receptors with almost limitless specificities
• Some of these receptors may recognise self-antigen
• Negative selection


  Central tolerance ensures that lymphocytes that recognise self-antigen with high avidity are removed
• Central tolerance is not perfect and some self-reactive lymphocytes can escape